1. Field of the Invention
The invention relates to the use of macrolide compounds, such as FK 506, for treatment of liver diseases and for regeneration of liver tissue. More specifically, the invention relates to the use of macrolide compounds to promote liver hypertrophy and hyperplasia and thereby facilitate regeneration of liver tissue.
2. Discussion of the Background
Immunosuppressive agents such as azathioprine, adrenocortical steroids and cyclosporin are used to suppress the immune system during organ transplant operations. Azathioprine and the adrenocortical steroids are also known to depress the regeneration of liver tissue after partial hepatectomy (Gonzalez et al, Surgery, 1970, 68:254-59 and Guzek, Nature, 1964, 201:930-31). In contrast, cyclosporin facilitates hepatic regeneration in both rats and dogs. (Makowka et al, Surg Forum, 1986, 37:352-54; Kahn et al, Transplant Proc, 1988, 20 (Suppl 3):850-52; Kim et al, Surg Gynecol Obstet, 1988, 166:317-22; Mazzaferro et al, Surgery, in press.
Macrolide compounds, in particular the macrolide FK 506, are known immunosuppressive compounds which prevent acute and chronic liver allograft rejection in humans more reliably and completely than has been possible with previous compounds (Starzl et al, Lancet, 1989, 2:1000-1004). Several compounds belonging to this class of immunosuppressive macrolides are obtained from cultures of species belonging to the genus Streptomyces. Compounds within this class are described in U.S. patent application Ser. Nos. 06/799,855, filed Nov. 20, 1985, 06/868,749, filed May 30, 1986 and 07/386,233. filed Jul. 28, 1989.
The ability of immunosuppressive drugs to facilitate liver regeneration is important to patient survival following transplant operations. Liver restoration is also important in the recovery of liver tissue following severe liver disease. Accordingly, a need continues to exist for improved methods of facilitating liver regeneration.